1. Field of the Invention
This invention relates to the field of devices useful for containing and analyzing blood for carrying out coagulation studies and other chemistry procedures, and a method for carrying out the procedures, including monitoring oral anticoagulant therapy to take into account the platelet count in determining prothrombin times (PT), International Normalized Ratios (INR), and partial thromboplastin times (PT).
2. Description of the Prior Art
Handling of human blood and body fluids in open containers carries with it the potential danger of the transmission of HIV (AIDS), Hepatitis B, Hepatitis C and other blood-borne diseases. It is desirable to avoid all human contact with blood. Existing coagulation and chemistry systems have capped holders for the blood which commonly comprise a stoppered tube containing a vacuum therein. One such example of a vacuum tube is the VACUTAINER(copyright) (Becton Dickinson). A needle apparatus is used in connection with the container to aspirate a fixed, known quantity of blood or blood plasma by piercing the container cap. The quantity of blood or plasma is then dispensed into open cuvettes where reactions take place. Automatic methods exist to dispose of the spent reactant cuvettes, but the cuvettes, too, are open. This open system has the potential for exposing blood to medical personnel.
In carrying out analyses of human blood, there exist certain inherent risks to those individuals, in particular, medical personnel, who handle the blood containers. The blood borne diseases, if not contained, can be deleterious to the health of those coming into contact with the blood. Blood is generally sampled from humans using a syringe and needle. The needle is inserted into a blood vessel or a catheter through which blood is withdrawn. It is the common practice to withdraw the blood through the needle and deliver the blood from the needle into a sample tube in which the blood can be temporarily stored for transport to the lab.
It is a common practice for a lab technician to remove blood from a sample tube, such as a cuvette, and then perform the appropriate analyses on the blood sample. Often, the testing involves mixing the blood with reagents, and undertaking studies of transformation of blood components, and production of components from enzymes. When the blood tube is opened, or when blood is removed from the tube, there is a risk of spilling the blood, or a risk of human contact with the blood. While medical personnel attempt to guard against these risks by wearing protective gear, such as gloves, face shields, lab coats, and other coverings, the risk of spillage remains. Furthermore, in some cases, due to the cumbersome coverings, gloves, lab coats, shields, and the like, carrying out testing is impeded, and sometimes, the protective coverings worn by individuals must be removed, and then replaced.
While robotics have been employed to facilitate processing of a blood sample. It is known to withdraw blood into a sample container or vial and store the container with one or more other samples, for processing, where a robotic arm is used to withdraw an amount of fluid from the sample vial and transfer that amount to a second vial for further processing. In some cases, the sample contents are transferred from a second vial to yet a third vial for spectrophotometic analysis. The original fluid sample is therefore removed from a container and the risks of handling and spillage, even though done with a robotic apparatus, still have the potential to contaminate the environment outside of the original sample vial.
Similarly, disposal of open containers presents a further problem. Risks of human contact with blood and other body fluids are present during the disposal, since the open container holding the blood sample must be handled, or the blood or fluid sample which has been removed from a closed tube disposed of properly.
A need exists for an apparatus and device which reduces the risk of contacting blood, but at the same time permits test analyses to be carried out. The present invention provides a novel apparatus and method for containing blood at the point of its withdrawal from a source, and up to and throughout its testing, then disposal.
Testing of blood and other body fluids is commonly done in hospitals, labs, clinics and other medical facilities. For example, to prevent excessive bleeding or deleterious blood clots, a patient may receive oral anticoagulant therapy before, during and after surgery. To assure that the oral anticoagulant therapy is properly administered, strict monitoring is accomplished and is more fully described in various medical technical literature, such as the articles entitled xe2x80x9cPTs, PR, ISIs and INRs: A Primer on Prothrombin Time Reporting Parts I and IIxe2x80x9d respectively published November, 1993 and December, 1993 issues of Clinical Hemostasis Review, and herein incorporated by reference.
These technical articles disclose anticoagulant therapy monitoring that takes into account three parameters which are: International Normalized Ratio (INR), International Sensitivity Index (ISI) and prothrombin time (PT), reported in seconds. The prothrombin time (PT) indicates the level of prothrombin and blood factors V, VII, and X in a plasma sample and is a measure of the coagulation response of a patient. The INR and ISI parameters are needed so as to take into account various differences in instrumentation, methodologies and in thromboplastins"" (Tps) sensitivities used in anticoagulant therapy. In general, thromboplastins (Tps) used in North America are derived from rabbit brain, those previously used in Great Britain from human brain, and those used in Europe from either rabbit brain or bovine brain. The INR and ISI parameters take into account all of these various different factors, such as the differences in thromboplastins (Tps), to provide a standardized system for monitoring oral anticoagulant therapy to reduce serious problems related to prior, during and after surgery, such as excessive bleeding or the formation of blood clots.
As reported in Part I (Calibration of Thromboplastin Reagents and Principles of Prothrombin Time Report) of the above technical article of the Clinical Hemostasis Review, the determination of the INR and ISI parameters are quite involved, and as reported in Part II (Limitation of INR Reporting) of the above technical article of the Clinical Hemostasis Review, the error yielded by the INR and ISI parameters is quite high, such as about 13%. The complexity of the interrelationship between the International Normalized Ratio (INR), the International Sensitivity Index (ISI) and the patient""s prothrombin time (PT) may be given by the below expression (1), wherein the quantity   [                    Patient        '            ⁢      s      ⁢              xe2x80x83            ⁢      PT              Mean      ⁢              xe2x80x83            ⁢      of      ⁢              xe2x80x83            ⁢      PT      ⁢              xe2x80x83            ⁢      Normal      ⁢              xe2x80x83            ⁢      Range        ]
is commonly referred to as prothrombin ratio (PR):                     INR        =                              [                                                            Patient                  '                                ⁢                s                ⁢                                  xe2x80x83                                ⁢                PT                                            Mean                ⁢                                  xe2x80x83                                ⁢                of                ⁢                                  xe2x80x83                                ⁢                PT                ⁢                                  xe2x80x83                                ⁢                Normal                ⁢                                  xe2x80x83                                ⁢                Range                                      ]                    ISI                                    (        1        )            
The possible error involved with the use of International Normalized Ratio (INR) is also discussed in the technical article entitled xe2x80x9cReliability and Clinical Impact of the Normalization of the Prothrombin Times in Oral Anticoagulant Controlxe2x80x9d of E. A. Loeliger et al, published in Thrombosis and Hemostasis 1985; 53: 148-154, and herein incorporated by reference. As can be seen in expression (1), ISI is an exponent of INR which leads to the possible error involved in the use of INR to be about xc2x113.5% or possibly even more. A procedure related to the calibration of the ISI is described in a technical article entitled xe2x80x9cFailure of the International Normalized Ratio to Generate Consistent Results within a. Local Medical Communityxe2x80x9d of V. L. Ng et al, published in Am. J. Clin Pathol 1993; 99: 689-694, and herein incorporated by reference.
The unwanted INR deviations are further discussed in the technical article entitled xe2x80x9cMinimum Lyophilized Plasma Requirement for ISI Calibrationxe2x80x9d of L. Poller et al published in Am J Clin Pathol February 1998, Vol. 109, No. 2, 196-204, and herein incorporated by reference. As discussed in this article, the INR deviations became prominent when the number of abnormal samples being tested therein was reduced to fewer than 20 which leads to keeping the population of the samples to at least 20. The paper of L. Poller et al also discusses the usage of 20 high lyophilized INR plasmas and 7 normal lyophilized plasmas to calibrate the INR. Further, in this article, a deviation of +/xe2x88x9210% from means was discussed as being an acceptable limit of INR deviation. Further still, this article discusses the evaluation techniques of taking into account the prothrombin ratio (PR) and the mean normal prothrombin time (MNPT), i.e., the geometric mean of normal plasma samples.
The discrepancies related to the use of the INR are further studied and described in the technical article of V. L. NG et al entitled, xe2x80x9cHighly Sensitive Thromboplastins Do Not Improve INR Precision,xe2x80x9d published in American Journal of Clinical Pathology, 1998; 109, No. 3, 338-346 and herein incorporated by reference. In this article, the clinical significance of INR discordance is examined with the results being tabulated in Table 4 therein and which are analyzed to conclude that the level of discordance for paired values of individual specimens tested with different thromboplastins disadvantageously range from 17% to 29%.
U.S. Pat. No. 5,981,285 issued on Nov. 9, 1999 to Wallace E. Carroll et al., which discloses a xe2x80x9cMethod and Apparatus for Determining Anticoagulant Therapy Factorsxe2x80x9d provides an accurate method for taking into account varying prothrombin (PT) times caused by different sensitivities of various thromboplastin formed from rabbit brain, bovine brain or other sources used for anticoagulant therapy. This method does not suffer from the relatively high (13%) error sometimes occurring because of the use of the INR and ISI parameters with the exponents used in their determination.
This invention relates to the inventions disclosed in U.S. Pat. Nos. 3,905,769 (""769) of Sep. 16, 1975; U.S. Pat. No. 5,197,017 (""017) dated Mar. 23, 1993; and U.S. Pat. No. 5,502,651 (""651) dated Mar. 26, 1996, all issued to Wallace E. Carroll and R. David Jackson, and all of which are incorporated herein by reference. The present invention provides an apparatus for containing and carrying out reactions and analyses on blood and other body fluids. The invention has particular utility for monitoring anticoagulant therapy, as well as other blood and fluid analyses.
The method and apparatus according to the present invention are useful for processing coagulation studies, and other chemistry procedures involving blood or other body fluids. The apparatus and method, in accordance with a preferred embodiment of the present invention, are used to determine anticoagulant therapy factors which are designated herein, in particular, prothrombin times (PT), International Normalized Ratios (INR) and modified ATF (MATF), corrected ATF (CATF) and are dependent on the prothrombin time (PT), the prothrombin ratio (PR), a fibrinogen transformation rate (FTR), and a maximum acceleration point (MAP) having an associated time to maximum acceleration (TMA). The anticoagulant therapy factors"" rates comprise a predetermined range starting prior to and ending after a maximum acceleration point which corresponds to the maximum acceleration of the fibrinogen (FBG) to fibrin conversion.
A further object of the present invention is to provide a method and apparatus for carrying out analyses to obtain corrected ATF (CATF) and modified ATF (MATF) values.
In accordance with the present invention, there is provided an apparatus and method for containing fluids, such as blood and other body fluids, and processing the fluids to carry out coagulation studies and other chemical procedures and analyses. A container device is provided which can receive and contain fluid from the point of withdrawal, from a body, contain the fluid throughout the processing and testing procedures and can be disposed of with the fluid after testing has been completed. In a preferred embodiment of the invention, the container means is a container having optically clear sides surrounding the container space, with a cover sealing off an opening of the container, and a reagent within the sealed container space, such as an anticoagulant reagent.
In carrying out coagulation studies it is important to isolate red blood cells (and white blood cells and platelets) from plasma. The device constructed in accordance with a preferred embodiment of the present invention is useful for coagulation studies. For example, a device constructed in accordance with the present invention is provided to receive and hold withdrawn blood as well as reagents. The separation of plasma and red blood cell components can be accomplished without removing the blood from the container.
Further, the invention provides a monitoring system for monitoring the blood and its components, along with reagents and other material contained in the sample container of the present invention. A computer is provided to store and integrate data collected by the monitoring system. The monitoring system, in accordance with a preferred embodiment of the present invention, has an optical emitter and a photo cell for taking spectropotentiophotometric readings of the contents of the sample container.
It is an object of the present invention to provide an apparatus for containing a body fluid such as blood, from the point of withdrawal of a body and during chemical processing and analyses so that removal of blood from the container is not necessary.
It is another object of the present invention to accomplish the above object by providing an optical reading device for determining optical measurements associated with blood and fluid samples while the blood and fluid samples are contained in the sample container into which they were originally drawn.
It is another object of the present invention to provide a sample container which has a chemical contained therein and can receive and contain a sample of fluid withdrawn from a body.
It is another object of the present invention to accomplish the above object where the chemical contained in the container is a blood preserving chemical.
It is another object of the present invention to provide an apparatus for analyzing blood and fluids as they sit in a sample container into which the blood and fluid were originally sampled from a body.
It is another object of the present invention to provide a method for carrying out blood analysis where fluid, such as blood, is withdrawn from its source (i.e., a human body), into a container device where it remains throughout testing and analysis and disposal.
It is another object of the present invention to provide a method and apparatus for carrying out coagulation studies and other chemical processes, where the fluid being studied and analyzed is permitted to remain in the apparatus from the time of its withdrawal, throughout testing and analysis, and when disposed of.
It is another object of the present invention to provide a novel method and apparatus for handling and processing blood and other body fluids which has improved safety features that reduce the risk of contact with the blood and fluids by medical personnel.
It is another object of the present invention to provide a novel method and apparatus useful for monitoring anticoagulant therapy.
It is another object of the present invention to carry out the above objects where the apparatus contains a silicone compound and an anticoagulant buffer predisposed in the apparatus for contact with fluid to be contained therein.
It is another object of the present invention to accomplish the above objects by providing a container device having a sealable opening which prevents container contents from exiting the container but permits the selective entry of reagents and other compounds into the container.